Acute experimental colitis and human chronic inflammatory diseases share expression of inflammation-related genes with conserved Ets2 binding sites.
BACKGROUND
Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by chronic inflammation of the gastrointestinal tract, with overlapping clinical characteristics and unknown etiology. We reasoned that in intestinal inflammation the initial activation of the innate immune response fails to resolve, finally resulting in uncontrolled chronic inflammatory bowel disease.


METHODS
To identify the early inflammatory events in colitis that remain active in human chronic colitis, we analyzed the changes of the colonic transcriptome during acute experimental colitis and compared the outcome with previously published profiles of affected tissues from patients with UC and CD, and as a control for intestinal inflammation in general, tissues from celiac disease patients. Rheumatoid arthritis synovial tissues were included as a nonintestinal inflammatory disease. The expression profiles of each disease were analyzed separately, in which diseased tissues were compared to unaffected tissues from the same anatomical location.


RESULTS
Gene ontology analysis of significantly regulated genes revealed a marked activation of immunity and defense processes in all diseases, except celiac disease, where immune activation is less prominent. The control region of upregulated genes contained an increase in Ets2 binding sites in experimental colitis, UC, and rheumatoid arthritis, and were associated with upregulated immune activity. In contrast, upregulated genes in celiac disease harbored the transcription factor binding site GLI, which binds to the Gli family of transcription factors involved in hedgehog signaling, affecting development and morphogenesis.


CONCLUSIONS
Ets2 may be an important transcription factor driving inflammation in acute as well as chronic inflammatory disease
van der Pouw Kraan
Tineke C T M
TC
VU University Medical Center, Department of Molecular Cell Biology & Immunology, Amsterdam, The Netherlands.
Zwiers
Antonie
A
Mulder
Chris J
CJ
Kraal
Georg
G
Bouma
Gerd
G
D000818:Animals; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics*
C494069:ETS2 protein, human; D050787:Proto-Oncogene Protein c-ets-2